Several recent advances in our understanding of the pathogenetic mechanisms underlying HIV dementia raise the possibility that factors other than direct infection may play a role in the development of neural cell dysfunction. Clinically dementia is associated with increased TNF-alpha in the brain, but decreased IL-1 beta. Intervention at the level of TNF-alpha appears to be a highly promising potential means of arresting the pathophysiology resulting in HIV cognitive and motor impairment. CPI-1189, an investigational drug for the treatment of Parkinson's disease and AIDS-related dementia complex, protects neuronal cells from TNF-alpha induced apoptosis and cell death in an in vitro primary human cell culture model which mimics the neuropathology associated with HIV dementia. A total of sixty subjects at six centers will be randomized to three groups. Twenty subjects will receive placebo for 10 weeks; 20 will receive 50 mg/day CPI-1189 for 10 weeks maintenance phase, subjects may enter a 12-week open-label follow-on phase during which CPI-1189 may be taken at a dose of up to 100 mg/day.